Search PubMed⌕ Search

Biomedical subjects

Mario Plebani

Publications and source records attributed to Mario Plebani.

At least 73 records · Page 4Linked to original sources
PubMed2004

Anti-heparan sulphate antibodies and homocysteine in dementia: markers of vascular pathology?

Increasing evidence supports a pathogenic role of heparan sulphate (HS) in the development of dementia. Since HS proteoglycans are present in the endothelial cells and perivascular basement membrane, we wanted to assess blood titres of HS antibodies (Abs) in patients with vascular dementia (VD) and in patients with Alzheimer's disease (AD) with cerebrovascular disease (CVD) [mixed dementia (MixD)]. Moreover, plasma levels of homocysteine, an independent risk factor for the development of dementia as well as for CVD, were also determined. High HS Abs titres were present in one patient with VD and in two patients with mixed dementia, as well as in two neurological control patients (stroke and epilepsy). Increased homocysteine levels were found in 62.5% of patients with mixed dementia, in 22.2% of the VD subjects, in 54.2% of patients with CVD, and in 41.2% of patients with other neurological diseases. The present findings suggest that neither elevated HS Abs titres nor increased homocysteinemia may represent a useful biochemical marker for the diagnosis of VD.

Adolescent↗
PubMed2004

Effect of inhalation of thermal water on airway inflammation in chronic obstructive pulmonary disease.

Thermal water inhalations have been traditionally used in the treatment of upper and lower chronic airway diseases. However, the benefit and the mechanism of this treatment have not been properly assessed. To determine whether inhaled salt-bromide-iodine thermal water improves lung function, quality of life and airway inflammation, 39 patients with chronic obstructive pulmonary disease (COPD) were randomly assigned to receive 2-weeks inhalation treatment with thermal water (active, no. = 20) or normal saline (control, no. = 19) in single blind. Lung volumes were measured, Saint George's respiratory questionnaire (SGRQ) was administered and induced sputum was performed before and after treatment. No changes in pre- and post-salbutamol lung volumes was observed after inhalation treatment in both groups. SGRQ score showed a significant improvement in active group compared with control group at the end of the trial. The concentration of total cells in induced sputum increased significantly in both active (P < 0.05) and control groups (P < 0.05). Inhalation of thermal water induced a small but significant decrease in percentages of sputum neutrophils (P < 0.01) and a parallel increase in macrophages (P < 0.01). In contrast, normal saline inhalation was not associated with changes in differential sputum cell counts. In conclusion, treatment with inhaled salt-bromide-iodine thermal water in COPD is associated with a reduced proportion of neutrophils in induced sputum suggesting that thermal water may have a mild anti-inflammatory effect on the airways. However, the short-term improvement in some components health-related quality of life was not related with changes in lung function or with the degree of airway inflammation.

Administration, Inhalation↗
PubMed2004

Pro- and anti-inflammatory cytokines gene polymorphisms and Helicobacter pylori infection: interactions influence outcome.

The aim of this study was to evaluate whether there was any correlation between Helicobacter pylori-associated diseases and (1) H. pylori virulence genes or (2) IL-1B, IL-1RN, IFN-G, TNF-A, IL-10 genetic polymorphisms. Patients with non-cardia gastric cancer (NCGC, n=129) or benign gastroduodenal diseases (n=792) were studied. IL-1RN intron 2 VNTR polymorphism (PCR), IL-1B -31 C/T (RFLP), the SNPs of IFN-G (+874 A/T), TNF-A (-1031 C/T, -857 C/T, -376 A/G, -308 A/G, -238 A/G), IL-10 (-1082 A/G, -819 C/T, -592 A/C) (Taqman chemistry) were studied. cagA, s1 and m1 vacA, were PCR amplified. Duodenal ulcer was more frequent in TNF-A -857 TT and in IL-1RN 1,2 subjects. TNF-A -857 TT genotype was also correlated with gastric ulcer. IL-10 -819 TT genotype was associated with intestinal metaplasia and NCGC. Antral inflammation was associated with TNF-A -1031 TT, while corpus activity with IL-10 -819 CC. H. pylori infection was associated with TNF-A -308 AG genotype, while IFN-G +874 AA genotype was associated with cagA. In conclusion, among host genetic factors contributing to H. pylori disease outcome, IFN-G +874 AA genotype favors cagA positive infections, TNF-A -857 TT duodenal ulcer while IL-10 -819 TT intestinal metaplasia and NCGC.

Adolescent↗
PubMed2004

Requirements for improving quality in the measurement of bone markers.

BACKGROUND: A number of biochemical assays readily detect molecules released from the bone matrix and collagen degradation in both serum and urine specimens. The variability of bone biochemical markers is still an issue of practical concern limiting their wider clinical use, and compromising the management of the individual patient. The aim of the present study was to define quality specifications of bone markers measurement in the total testing process. METHODS: The different sources of biological variability of biochemical bone marker were assessed according to the current knowledge and categorized as pre-analytical, intra-analytical and post-analytical. RESULTS: The identification of factors influencing bone marker measurements allowed recommendations to be made for decreasing pre- and intra-analytical variation in order to improve laboratory performance. The assessment of post-analytical sources of variation, moreover, involves the practical use of bone markers in identifying individual women at risk of fractures and the identification of non-responders, providing adequate limit value, least significant change value or optimal threshold of bone marker change. CONCLUSIONS: Laboratory services may improve the potential clinical applications of biochemical markers of bone remodeling by improving method standardization, defining and reducing pre-analytical and analytical variables and providing reports that specify analytical and biological variation or cut-off values, thus facilitating data interpretation or reports.

Analysis of Variance↗
PubMed2004

Quality specifications in EQA schemes: from theory to practice.

BACKGROUND: External quality assessment (EQA) is a tool for quality management in clinical laboratories and its main objectives are assessment of participants and methods performance, training and advice. This paper describes the quality specifications used in EQA schemes of the Centre of Biomedical Research (CRB), in order to design schemes that can assess laboratory reliability performances, meet the changing needs and quality recommendations. METHODS: Quality specifications for control materials, statistical procedures and goals to assess laboratory performance have been applied and introduced in EQA schemes managed by CRB. RESULTS: The application of well-defined quality specifications has demonstrated effective. In particular, we report results on alkaline phosphatase and cholesterol obtained using commercial control materials and human serum controls, in two different EQA surveys; the inter-laboratory variability (CVinter%) for troponin I analysed with a diagnostic system and assigned values of CK-MB mass obtained using four different diagnostic systems; the percentage of acceptable performances obtained by means of the application of goals based on clinical criteria, biological variation, state-of-the-art and used for EQA schemes, and referring to some analytes with significant clinical values such as cholesterol, glucose, glycated hemoglobin and sodium. CONCLUSIONS: The design of reliable EQA schemes based on evidence-based quality specifications is a pre-requisite for supporting the quality improvement of clinical laboratories.

Alkaline Phosphatase↗
PubMed2004

What information on quality specifications should be communicated to clinicians, and how?

BACKGROUND: Quality specifications, the level of performance required to facilitate clinical decision-making, not only have a central role in quality management in the laboratory but are also essential for assuring the interpretation and utilization of laboratory data by physicians. Consensus has been reached on the hierarchy of criteria for quality specifications. However, the information on quality specifications that should be communicated to clinicians, and the way in which this information should be given, is still widely debated. METHODS: Laboratory tests have been grouped into four categories including uni-modal, and bi-modal distributions, tests used in patients monitoring and in evaluating the response to therapy (serial measurements), and, finally, tests that require interpretive comments. The most suitable and informative ways to communicate quality specifications to clinicians have been proposed for each category. RESULTS: For tests with a uni-modal distribution, the decision limits should replace traditional reference values in the report. For tests with a bi-modal distribution, in addition to traditional reference values, some flags based on the uncertainty (i.e., analytical and biological variability) of laboratory data, can be included to help clinicians interpret laboratory data. For tests used in monitoring patients and in evaluating the response to therapy (serial measurements), the reference change value or the most effective threshold of the difference between two consecutive results should be indicated. For tests/test batteries that require interpretive comments, these should be added to the report and discussed in multidisciplinary meetings and interpretive rounds to promote knowledge of a more objective evaluation of laboratory data. CONCLUSIONS: A proposal has been made to improve the way laboratory results are communicated to clinicians, with practical information derived from quality specifications. By providing clinicians with information on quality characteristics and the degree of uncertainty, a more objective interpretation of laboratory data may be possible, and data may be more appropriately utilized for diagnosis and monitoring.

Clinical Chemistry Tests↗
PubMed2004

Cord blood cardiac troponin T and troponin I levels in multiple-gestation neonates.

The increased mortality and morbidity rates in multiple-gestation neonates are not completely understood. Troponin measurements have a role in situations where the evaluation of the cardiac damage is difficult, such as in cases of unexplained intrauterine fetal growth restriction or death. These conditions, along with perinatal hypoxic risk and in utero ischemic damage, are frequently found in multiple gestations. In this context, a myocardial damage could be expected more frequently in multiple than in singleton births. We hypothesized that cord blood cardiac troponin T and troponin I, markers of myocardial damage, could be different between singleton and multiple pregnancies and, among twins, between the first- and the second-born twin. Troponins T and I and creatine kinase MB concentrations were not increased in twins at birth and were not different between the first- and the second-born twin. These data suggest that myocardial damage, evaluated by cardiac troponin T, troponin I, and creatine kinase MB measurements, does not seem to be a relevant problem in multiple-gestation neonates.

Birth Order↗
PubMed2004

Maldi-TOF analysis of portal sera of pancreatic cancer patients: identification of diabetogenic and antidiabetogenic peptides.

BACKGROUND: Pancreatic cancer (PC) associated diabetes mellitus (DM) might be consequent to the diabetogenic effects of tumour products, possibly acting via nitric oxide (NO). Our aims were: (1) to verify whether PC associated DM determines an increased hepatic NO and (2) using MALDI-TOF analysis, to evaluate the peptide composition of PC cell conditioned media (CM) and of portal sera from patients with PC with (n=7) or without (n=4) DM. METHODS: In liver tissue homogenates of 23 patients with PC (n=17) or chronic pancreatitis (n=6) GAPDH mRNA and activity, glucose, lactate, nitrite and nitrate were assayed. MALDI-TOF analysis was performed in three PC cell lines CM, and in portal sera from patients with PC. RESULTS: Higher GAPDH mRNA and nitrite were found in patients with than in patients without DM. In PC cell CM, only 9 among a total of 75 fragments identified, were tumour specific. One hundred seventy-three fragments were identified in the portal sera of patients: one was positively and six fragments were negatively correlated with DM. CONCLUSIONS: Unlike liver GAPDH, NO appears to be involved in PC associated DM. In portal sera, the absence, rather than the presence, of specific fragments, appears to be correlated with the development of DM.

Aged↗
PubMed2004

Clinical significance of alpha-fetoprotein mRNA in blood of patients with hepatocellular carcinoma.

BACKGROUND: Alpha-fetoprotein (AFP) messenger RNA (mRNA) in the blood reflects the presence of circulating hepatocellular carcinoma (HCC) cells and is a sensitive marker of HCC extrahepatic metastases. The specificity of this molecular marker and its correlation with the main HCC clinical-pathological parameters remains controversial, however. METHODS: AFPmRNA was determined in 50 HCC patients and in 50 patients with diagnosis of cirrhosis (6), or colon (24) or, pancreatic (20) carcinoma. HCC patients with clinically evident extrahepatic metastasis were excluded. HCC diagnosis was confirmed in all patients by histology on percutaneous biopsies or surgical specimens; pathological grading was assessed at the same time. RESULTS: AFPmRNA was positive in 20 HCC patients (40%) and in 18 patients without HCC (36%). The presence of AFPmRNA in the blood correlated significantly with cholestatic indices (p<0.01), nodule size (p=0.03), vascular invasion (p=0.006) and moderately or poorly differentiated HCC (p<0.0001). Moreover, survival analysis showed a significant impact of AFPmRNA detection on overall (p=0.04) and recurrence-free survival (p=0.0007) after a median follow-up of 17 months. CONCLUSIONS: Although AFPmRNA is frequently detected in the blood, even in benign liver diseases or gastroenteric tumors, in HCC patients without clinical evidence of extrahepatic metastases it seemed to identify the biologically more aggressive tumors.

Adult↗
PubMed2004

Non-invasive diagnosis of Helicobacter pylori infection: simplified 13C-urea breath test, stool antigen testing, or DNA PCR in human feces in a clinical laboratory setting?

OBJECTIVES: (1) To compare two stool antigen EIAs (HpSA, FemtoLab) and PCR of ureaseA and cagA in feces, with (13)C-urea breath test (UBT). (2) To ascertain whether a simplified UBT (breath collection time = 10 min) is as reliable as the standard assay (30 min). DESIGN AND METHODS: Helicobacter pylori status was recorded in Group 1 (n = 187) by UBT, H. pylori stool antigen, ureA and cagA PCR in feces. UBT with 10, 20 and 30 min sampling was performed in Group 2 patients (n = 283). RESULTS: The sensitivity and specificity of HpSA, FemtoLab, and ureA were 67% and 99%, 90% and 96%, 35% and 98%, respectively. cagA results were positive in 16/48 H. pylori-positive, and in 5/100 H. pylori-negative patients. The results of UBT with a 10- and 30-min sampling strictly overlapped. CONCLUSION: UBT with 10 min breath collection and FemtoLab stool antigen assay are the most reliable non-invasive tests to diagnose H. pylori infection.

Adult↗
PubMed2004

H. pylori infection: bacterial virulence factors and cytokine gene polymorphisms as determinants of infection outcome.

The gram negative bacterium H. pylori infects the human stomach worldwide, invariably causing mucosal inflammation. In the majority of cases, H. pylori-associated gastritis remains the only clinical manifestation of the infection, which might cause, otherwise, peptic ulcer, gastric adenocarcinoma. or MALToma. The balance between the bacterial virulence machinery and the host response to the infection determines the different clinical outcomes. The main bacterial virulence factors comprise adhesins (BabA, SabA), the vacuolating cytotoxin VacA, and the products of cag pathogenicity island. The pattern of cytokine production in response to the infection is one of the main host determinants involved in limiting the infection outcome to gastritis or in favoring peptic ulcer or cancer onset. The polymorphisms of some cytokine genes (IL-1beta IL-1RN, TNF-alpha, IFN-gamma) have been correlated with H. pylori-associated gastric adenocarcinoma or peptic ulcer, possibly because they influence the amount of cytokine production in response to H. pylori infection. This review focuses on the role of H. pylori virulence genes and on host cytokines' genes polymorphisms in determining clinical outcome to H. pylori infection.

Animals↗
PubMed2004

Biochemistry and clinical role of human cystatin C.

Low molecular-mass plasma proteins play a key role in health and disease. Cystatin C is an endogenous cysteine proteinase inhibitor belonging to the type 2 cystatin superfamily. The mature, active form of human cystatin C is a single non-glycosylated polypeptide chain consisting of 120 amino acid residues, with a molecular mass of 13,343-13,359 Da, and containing four characteristic disulfide-paired cysteine residues. Human cystatin C is encoded by the CST3 gene, ubiquitously expressed at moderate levels. Cystatin C monomer is present in all human body fluids; it is preferentially abundant in cerebrospinal fluid, seminal plasma, and milk. Cystatin C L68Q variant is an amyloid fibril-forming protein with a high tendency to dimerize. It forms self-aggregates with massive amyloid deposits in the brain arteries of young adults, leading to lethal cerebral hemorrhage. The main catabolic site of cystatin C is the kidney: more than 99% of the protein is cleared from the circulation by glomerular ultrafiltration and tubular reabsorption. The diagnostic value of cystatin C as a marker of kidney dysfunction has been extensively investigated in multiple clinical studies on adults, children, and in the elderly. In almost all the clinical studies, cystatin C demonstrated a better diagnostic accuracy than serum creatinine in discriminating normal from impaired kidney function, but controversial results have been obtained by comparing this protein with other indices of kidney disease, especially serum creatinine-based equations. In this review, we present and discuss most of the available data from the literature, critically reviewing conclusions and suggestions for the use of cystatin C in clinical practice. Despite the multitude of clinical data in the literature, cystatin C has not been widely used, perhaps because of a combination of factors, such as a general diffidence among clinicians, the absence of definitive cut-off values, conflicting results in clinical studies, no clear evidence on when and how to request the test, the poor commutability of results, and no accurate examination of costs and of its routine use in a stat laboratory.

Cerebrospinal Fluid↗
PubMed2004

A large deletion due to a new mutation (intron 13/exon 23) in a sporadic case of severe hemophilia A.

A case of sporadic hemophilia A in a young child was investigated from a molecular biology point of view. The propositus is a 4-year-old severe hemophiliac who was first seen when he was 2 years old. At that time, easy bruising and hematomas were noted because of accidental falls while toddling. The coagulation study showed a prolonged partial thromboplastin time and a factor VIII level of 1.3% of normal. Molecular biologic analysis showed a large deletion involving intron 13 up to exon 23. In the inversion study, the propositus exhibited only a 10 kb band, and this result suggests that intron 22 was deleted while his mother shows a normal pattern. To further examine the length of the deletion, a long polymerase chain reaction by means of primers amplifying the region from exon 13 to 23. In the index patient, an approximate 13-kb product was obtained, whereas no product was obtained from his mother. The mother investigated by means of polymorphism was shown not to be a carrier.

Child, Preschool↗
PubMed2004

Amphetamines and 3,4-methylendioxymetamphetamine (MDMA): evaluation of KIMS (kinetic interaction of microparticles in solution) assay at two cut-off levels.

Two screening methods for the assay of amphetamines and their derivatives have been applied to the same analytical instrument for their evaluation. In addition to an assay at a cut-off of 1000 microg/l, a new specific reagent was evaluated for an ultra-sensitive assay of amphetamines and 3,4-methylendioxymetamphetamine with a cut-off of 300 microg/l. The assay confirmation was performed using high-performance liquid chromatography and gas chromatography/ mass spectrometry techniques. The results were positive for both screening methods, confirming the efficacy of two simultaneous methods with different cut-off levels.

3,4-Methylenedioxyamphetamine↗
PubMed2004

External quality assessment for biochemical markers of myocardial damage: an Italian experience.

In 1999 the Centre of Biomedical Research (CRB) in co-operation with the Italian interdisciplinary and intersociety Working Group on Markers of Myocardial Damage proposed a national external quality assurance scheme that was granted in accordance with the UK Clinical Pathology Accreditation Standards in 2001. The scheme, which stresses the importance of educational aspects in quality assurance, was scientifically designed to ensure that it would provide an objective assessment of participants' performance and promote quality improvements to meet the needs of participants. The present paper reports on the data collected in EQA cycles conducted to evaluate improvements in the performance of participants and in related methods. The findings obtained demonstrate that during the 4-year experience the scheme provided opportunities to improve the performance of laboratories and promoted an efficient, more satisfactory approach to analytical aspects. The number of unacceptable performances decreased from 11.6% to 5.6% for troponin I, from 19.5% to 9.0% for myoglobin and from 13.2% to 4.3% for creatine kinase myocardial isoenzyme (CK-MB). During cycles in 2001 and 2002, inter-variability (coefficient of variation, CV%) data for all markers appeared satisfactory and showed a significant improvement (lower than 10%), in particular for procedures automated on Dade Behring Dimension and Beckman Access systems. However, reference values/decisional limits declared by laboratories and those suggested by the manufacturers are not comparable, even within the same diagnostic system. The findings demonstrate that participation in EQA schemes provided an opportunity for participating laboratories to continuously improve the quality of their services.

Biomarkers↗
PubMed2004

Plasma levels of tumor necrosis factor-alpha correlate with the six-minute walk test results in patients with mild to moderate heart failure.

BACKGROUND: The plasma levels of brain natriuretic peptide, tumor necrosis factor-alpha, big endothelin-1 and cardiac troponins have been reported to correlate with the severity of heart failure. METHODS: In a single population of 80 outpatients with mild to moderate chronic heart failure the correlation between the patient's functional capacity, as evaluated at a 6-min walk test, the clinical parameters and plasma levels of brain natriuretic peptide, tumor necrosis factor-alpha, big endothelin-1 and cardiac troponins was evaluated. RESULTS: A significant inverse correlation was found with the patient's age (p < 0.0001), NYHA functional class (p < 0.0001), left ventricular dysfunction etiology (ischemic vs dilated cardiomyopathy, p < 0.0005), heart rate (p < 0.05), plasma levels of brain natriuretic peptide (p < 0.05) and of tumor necrosis factor-alpha (p < 0.0005). At multiple regression analysis a correlation was found between the 6-min walk test results and the patient's age (p < 0.05), NYHA functional class (p < 0.01), left ventricular dysfunction etiology (ischemic vs dilated cardiomyopathy, p < 0.05) and tumor necrosis factor-alpha plasma levels (p < 0.05). CONCLUSIONS: In our patients with mild to moderate heart failure, a significant correlation was found between the results of the 6-min walk test and only the plasma concentrations of tumor necrosis factor-alpha among the laboratory parameters analyzed in this study.

Adult↗